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Regulation of Neuronal Chemokine Receptor CXCR4 by μ-Opioid Agonists and Its Involvement in NeuroAIDS

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Chemokine Receptors and NeuroAIDS

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Abstract

The chemokine CXCL12 (formerly known as SDF1-α) and its receptor CXCR4 play a pivotal role in the developing and mature central nervous system. CXCR4 is widely expressed in the brain, in areas such as the cerebellum, cortex, hypothalamus, hippocampus, and brain stem. In vivo as well as in vitro studies have confirmed the expression of both CXCL12 and CXCR4 in most CNS cell types including neurons, astrocytes and microglia. CXCL12 and CXCR4 play a crucial role during CNS development and are also involved in maintaining neuro-glial function in the adult brain. CXCL12 binding to CXCR4 leads to the activation of a number of signaling pathways some of which are critical to neuronal survival. However, under certain unique extracellular conditions, CXCR4 activation can also induce cell death. For example, CXCR4 can also interact with the HIV-1 envelope glycoprotein gp120 with signaling outcomes leading to neuronal cell death. Furthermore, cellular and environmental factors affecting either CXCL12 or CXCR4 can also modulate receptor activation and neuronal survival. Given the crucial role of the chemokine and its receptor in the development and maintenance of CNS homeostasis, factors affecting CXCL12/CXCR4 signaling may thus ultimately alter brain physiology. For instance, evidence in literature indicates that CXCL12/CXCR4-induced pathways are targets of opioids and other commonly abused drugs. A negative, bi-directional cross-talk between opioid and chemokine receptors has been observed in both immune and central nervous system. However, the molecular mechanisms involved in such interactions and their clinical consequences are largely unknown. This chapter will review our current knowledge on the cross-talk between opioid and chemokine receptors in the brain focusing on underlying cellular and molecular mechanisms which might be relevant to HIV neuropathology.

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Acknowledgments

The authors thank the National Institute of Health and National Institute of Drug Abuse for their continuous support (grants DA15014 & DA19808).

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  1. Departments of Pharmacology and Physiology & Microbiology and Immunology, Drexel University College of Medicine, 245 N 15th St. New College Building, 8804, Philadelphia, PA, 19102, USA

    Rajarshi Sengupta & Olimpia Meucci

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  1. Rajarshi Sengupta
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  2. Olimpia Meucci
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Correspondence to Olimpia Meucci .

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  1. Dept. Pharmacology & Physiology, & Institute of Molecular Medicine, Drexel University College of Medicine, North 15th St. 245, Philadelphia, 19102-1101, USA

    Olimpia Meucci

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Sengupta, R., Meucci, O. (2010). Regulation of Neuronal Chemokine Receptor CXCR4 by μ-Opioid Agonists and Its Involvement in NeuroAIDS. In: Meucci, O. (eds) Chemokine Receptors and NeuroAIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0793-6_17

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